The present invention relates to a method of inducing hemostasis in mammals, and, in particular to providing a method for applying a highly effective hemostatic agent at a desired treatment site with a plasma fibrin and thrombin composition. The invention further relates to a kit suitable for the preparation and application of the hemostatic agent prepared in accordance with the present invention.
Plasma refers to the liquid portion of the blood in which the particulate components thereof are normally present. The chief components of plasma are proteins, anions, and cations. The proteins include albumin and globulins. Anions are chiefly chloride and bicarbonate, while cations are largely sodium, potassium, calcium and magnesium. Blood plasma also circulates immunoglobulins and several of the essential components for blood clot formation described in further detail below.
The clotting of blood as a part of the body's natural response to an injury or trauma is part of the natural phenomenon of hemostasis. Blood clot formation derives from a series of events called the coagulation cascade in which the final steps involve the formation of the enzyme thrombin. Thrombin converts circulating fibrinogen into fibrin, a mesh-like structure which forms the insoluble structure of the blood clot.
Normally, thrombin does not exist in the active state within the blood circulation system but rather in the form of an inactive precursor, prothrombin. Thrombin is activated, however, through one of two mechanisms commonly referred to as the extrinsic and intrinsic pathways. The pathways are schematically represented in FIG. 1.
The intrinsic pathway activates thrombin when blood contacts glass outside the body, as in a test tube or other negatively charged surfaces and is not pertinent to the subject of the present invention. The extrinsic pathway, on the other hand, activates thrombin when blood comes in contact with injured tissues which produce tissue thromboplastin. The interactions of tissue thromboplastin with naturally present calcium ions and several plasma proteins lead to the conversion of prothrombin to thrombin.
As a part of hemostasis, clot formation is often a life-saving process in response to trauma and serves to arrest the flow of blood from severed vasculature. In addition, it is often desirable to initiate or enhance the body's natural hemostatic process. For example, after severe trauma, a victim may require supplemental assistance in stopping bleeding or hemorrhage caused by the trauma. Alternatively, a physician may wish to initiate and/or enhance wound closure after surgery.
The use of exogenous thrombin as a clot-enhancing or hemostatic agent is known in the art. Thrombin of bovine origin is useful in surgery or emergency situations for local application in the control of minor oozing. Thrombin is applied topically as a powder or in a solution at the site of the wound.
The use of thrombin as a single agent for inducing clotting and hemostasis, however, is limited to minor clots or injuries. In more extensive bleeding or in hemorrhage, it is necessary to employ a matrix to hold the thrombin at the desired location and to provide a structure for clot formation. Matrix materials known in the art include fibrin foam-like compositions and gelatinous sponges. Even with such matrix materials, thrombin is generally regarded as ineffective for inducing coagulation and hemostasis on arterial bleeding.
An alternative approach to the use of thrombin as an adjunct in inducing coagulation involves the application of thrombin along with fractionated plasma at the wound site.
Fractionated plasma is obtained from either autologous or nonautologous blood sources at least several hours in advance of need, usually a day before, and is frozen, cryoprecipitated and then thawed before being combined with thrombin at the site of need. Recent concerns with the use of blood products obtained from sources foreign to the patient have severely limited the use of nonautologous plasma due to the possibility of disease transmission in spite of extensive precautions.
The use of fractionated plasma as a thrombin adjunct in promotion of therapeutic clotting is therefore significantly hampered by the methods of the prior art since the plasma must be obtained several hours and usually a day prior to its use. The problems are magnified when emergency situations arise and the several hour time lag for plasma fractionation is unavailable or otherwise impracticable.
The aforementioned approaches and techniques for inducing therapeutic clotting and coagulation therefore all fall short of providing a method for treating undesired bleeding in mammals. Thrombin alone is often insufficient and needs supplementation to be effective. Thrombin enhanced with cryoprecipitated fibrin obtained from plasma has several drawbacks. The most significant drawback to date has been the lengthy time delay between the drawing of blood and extraction of the plasma fibrin before end use. Nonautologous sources of blood plasma are now largely avoided since they expose the patient to the risk of contacting serious diseases transmitted by foreign blood products.
Accordingly, there exists a need for providing an improved method for treating undesired bleeding by inducing coagulation with thrombin and a plasma fibrin composition. There is also a need for providing the plasma fibrin for use with thrombin to induce clotting in a much more rapid manner than the prior art allows.
It is therefore an object of the present invention to provide a new and improved method for effecting therapeutic hemostasis and coagulation.
It is a further object of the present invention to provide such a method using whole plasma fibrin.
A still further object of the present invention is to provide such a method using autologous whole plasma fibrin which is obtained perioperatively.
Yet another object of the present invention is to provide a kit for the perioperative preparation of whole plasma fibrin and a thrombin solution for application on selected treatment sites.
A still further object of the present invention is to provide a means for applying whole plasma fibrin and thrombin solutions contained in separate vessels so that the whole plasma fibrin and thrombin initiate contact with each other at the site of the wound to effect coagulation.
Other objects and advantages will become apparent to those skilled in the art from a consideration of the ensuing description.